Evidence obtained using mouse models suggests that lymphocytes, particularly thymus-derived lymphocytes, are important contributors to the inflammatory lung disease which can be caused by influenza virus infection. This project is aimed at identifying the immunologic mechanisms influencing the development of the inflammatory response to this infection. Virus inocula to be used are two derivatives of influenza A/Hong Kong virus which are equally infectious for mice, but very different in their ability to cause pneumonia and death. Indices of infection and gross and microscopic quantitation of inflammation will be measured sequentially after inoculation of mice and correlated with the number, identity and functional competency of immunocytes from lung, bronchoalveolar lavage, thymus, spleen and peripheral nodes. Functional assays will include those for blastogenic response, lymphocyte-mediated cytotoxicity, direct migration inhibition, migration inhibiting factor, and chemotactic factor. Thymic atrophy accompanies severe influenza pneumonia in these mice, and functional changes and migration of thymocytes will be studied in infected intact, adrenalectomized and steroid-treated mice to evaluate the specificity of this response. Athymic nude mice develop little pneumonia when infected with virulent influenza virus, and the effect on this model of reconstitution with selected lymphocyte populations will be evaluated. The results of these studies and the contrast between the effects of infection with the 2 different influenza virus derivatives should aid in defining the interactions and importance of immunopathologic processes in virus-induced inflammation of the lung. BIBLIOGRAPHIC REFERENCE: (1) Wyde, P.R., Couch, R.B., Mackler, B.F., Cate, T.R., and Levy, B.M.: 1977. Effects of low- and high-passage influenza virus infection in normal and nude mice. Infect. Immun. 15:221.